This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. PglD is an essential enzyme in the N-linked glycoprotein biosynthetic pathway in the pathogenic bacteria Campylobacter jejuni. C. jejuni is the primary cause of gastroenteritis in humans and is the most frequent infection to precede the peripheral neuropathy Guillain-Barr[unreadable][unreadable] syndrome. It is known that the C. jejuni-specific protein glycosylation is disrupted in mutant bacteria lacking pglD, and that these bacteria are compromised in their ability to infect the host organism. In our lab we have initiated a project to develop an effective inhibitor of PglD by fragment-based screening. We have identified eleven small molecules (MW <300 Da, [unreadable][unreadable]Sfragments[unreadable][unreadable]?) which bind to PglD, and we seek to determine their binding mode by X-ray crystallography. The essential structural information will guide the development of tighter PglD binders which will be synthesized and evaluated in our laboratory. It is anticipated that this approach will result in a specific, nanomolar inhibitor of PglD. Armed with such a tool, we will be able to control N-glycosylation in vivo, thereby unraveling its biological roles. Such a compound will also be of therapeutic value.